Do we need legislation to ensure age representation?
Authors: None The Lancet Healthy Longevity
Journal: The Lancet Healthy Longevity (2023)

Older adults (aged >60 years) are the fastest growing demographic in the world and are prescribed more medications than any other age group. Studies have reported that, across multiple different countries and populations, older adults on average take between two and nine different medications every day. However, older adults are consistently underrepresented in clinical trials testing new medications, many of which are predominantly intended for this demographic. For example, older adults make up 56% of the global cancer population but constitute just 40% of participants in trials for new cancer therapies. Clinical trial cohorts must be representative of real-world populations, and age diversity is an overlooked aspect of this issue. Without representative population diversity, trials are fundamentally flawed and cannot generate sufficient evidence to show safety and efficacy of a drug in older populations. In April, two reports calling for diversity and inclusion mandates in clinical trials, with particular focus on older adults, were published. The first report, from the International Longevity Centre (ILC), urges for action to ensure that medicines are tested in the populations that they are supposed to help. The second report, from the Nuffield Council on Bioethics (NCOB), calls for action to embed an ethical approach that places diversity, values, and agency of older adults at the centre of all research and innovation related to ageing. The publication of both reports came just weeks after the US Food and Drug Administration's proposals to require diversity plans from researchers for clinical trials to be approved. Furthermore, the ILC and NCOB reports coincided with the introduction of new measures by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. These measures are predominantly aimed at supporting researchers in getting faster and easier approval to run clinical trials; however, they also come with comprehensive guidance outlining how to achieve diversity in trials in a way that is proportionate and achieves the best results. These new initiatives from the UK and USA are encouraging, but they both stop short of providing legislation for clinical trials. The MHRA state that guidance rather than legislation will ensure the flexibility necessary to reflect the many different types of clinical trials. In addition to calls for age diversity and inclusion, the NCOB propose strategies for tackling barriers hindering the participation of older adults in research studies. Although efforts have been made to remove barriers such as age-based exclusion criteria, it is still commonplace for studies to have exclusion criteria that, while not explicitly referencing age, inevitably preclude older adults from participating. For example, exclusion on the basis of multimorbidity disproportionately affects older populations. Similarly, concomitant medication and polypharmacy use is also a regular barrier to participation. Although multimorbidity and polypharmacy are undoubtedly challenging for trial designers, their inclusion is necessary for ascertaining accurate real-world data. Moreover, their exclusion drives disparities in treatment outcomes (eg, reduced effectiveness and increased side-effects) for older adults following drug approval. Given all the challenges, it is understandable that trial designers often choose the more straightforward path. By recruiting younger cohorts, researchers typically attain datasets that are less complex, from which it is easier to draw clear and concise—but potentially less accurate—conclusions. Furthermore, trials tend to be run on the assumption that it is more expensive to include older adults. Assumptions such as these, however, must be challenged, and accuracy valued over ease. It is important to recognise that older adults are a uniquely heterogeneous population. Factors such as frailty, multimorbidity, immune function, and metabolic clearance necessitate the assessment of differential drug effects in this demographic. Between 2015 and 2050, the proportion of the world's population that is older than 60 years will almost double from 12% to 22%. Inclusion of this rapidly growing population in clinical trials is the only way of ensuring that we have medications that are safe and efficacious. It is essential that we prioritise age diversity in clinical trials and work now to remove the remaining barriers preventing older adults from participating. To echo the ILC report, structural, cultural, and potentially legislative change will be needed to ensure that age-diverse representation becomes a reality.